Abstract: The nervous and immune systems exhibit numerous similarities within human oral tissues, as both systems are responsible for monitoring environmental and internal stimuli, integrating these signals to maintain homeostasis, and mediating defense responses against potential threats. Recent advancements have enhanced the mechanistic understanding of neuroimmune interactions in oral tissue, highlighting the crucial role of this crosstalk in maintaining oral tissue homeostasis and modulating inflammatory and infectious oral diseases. This review aims to elucidate the pivotal role of these interactions in the initiation and progression of oral disease. Interactions mediated by neurotransmitters and neuropeptides exert a significant influence on immune-cell function, while inflammatory mediators induce peripheral and central sensitization of sensory neurons that innervate the oral cavity. These processes are extremely important in the development and progression of oral conditions such as periodontitis, pulpitis, and oral cancer. In addition, we examine the interplay between the nervous and immune systems and provide new insights into potential therapeutic interventions to target neuroimmune pathways in oral health.